Retroviral vectors have proven useful in a variety of gene transfer applications. A key feature of their utility is the availability of retrovirus packaging cells that allow production of retroviral vectors in the absence of helper virus, and thus prevent spread of the vector in infected cells. Retrovirus packaging cells have been constructed based on ecotropic and amphotropic murine retroviruses, avian leukosis virus, and spleen necrosis virus (15). However, not all cell types can be efficiently infected by using the available packaging cell lines, and cells from several species of experimental importance are not easily infected, notably bovine and hamster cells. The range of cells that are infectable is primarily determined by the envelope protein of the virus and the presence of appropriate receptors for this protein on the surface of infected cells. For example, viruses that infect human cells can be separated into eight groups based on the use of different receptors for cell entry (28).
Gibbon ape leukemia virus (GaLV) uses an internalization receptor that is different from those of the available packaging cell lines. The same receptor is used by simian sarcoma associated virus (SSAV) (28), which is apparently a substrain of GaLV (5), the feline leukemia virus-B (FeLV-B) (28). The human receptor for GaLV has recently been cloned and shows a wide cell type and species distribution (22). Indeed, GaLV can infect many mammalian species (13), with the notable exception of mouse cells. Formation of infectious hybrid virions with GaLV and human T-cell leukemia virus retroviral env glycoproteins and the gag and pol proteins of Moloney murine leukemia virus (MoMLV) has recently been reported by Wilson et al. (30).
The advantages of stable packaging cell lines (as opposed to transiently cotransfected cells) include a reproducible source of high titer viral particles. In addition, packaging cell lines can be selected and cloned for desirable properties, such as stability of in vivo growth, lack of production of helper virus, lack of reinfection by viral particles packaged in the cell, stability from genetic rearrangement and recombinational events, resistance to complement lysis, and improved ability to infect cells from higher mammals. Thus, stable packaging cell lines based on GaLV would offer significant advantages over both transient cotransfected cells and the existing packaging cell lines based on amphotropic and ecotropic MuLV.